JP2008521858A - 過増殖性疾患を処置するための［１，２，４］トリアゾロ［４，３−ａ］ピリジン誘導体 - Google Patents
過増殖性疾患を処置するための［１，２，４］トリアゾロ［４，３−ａ］ピリジン誘導体 Download PDFInfo
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04028439 | 2004-12-01 | ||
| PCT/EP2005/012855 WO2006058752A1 (en) | 2004-12-01 | 2005-12-01 | [1,2,4]triazolo[4,3-a]pyridine derivatives for the treatment of hyperproliferative diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2008521858A true JP2008521858A (ja) | 2008-06-26 |
Family
ID=34927603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007543779A Pending JP2008521858A (ja) | 2004-12-01 | 2005-12-01 | 過増殖性疾患を処置するための［１，２，４］トリアゾロ［４，３−ａ］ピリジン誘導体 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20070299103A1 (de) |
| EP (1) | EP1828184B1 (de) |
| JP (1) | JP2008521858A (de) |
| AT (1) | ATE443063T1 (de) |
| AU (1) | AU2005311451A1 (de) |
| CA (1) | CA2586796A1 (de) |
| DE (1) | DE602005016718D1 (de) |
| ES (1) | ES2330872T3 (de) |
| IL (1) | IL183340A0 (de) |
| NO (1) | NO20073393L (de) |
| WO (1) | WO2006058752A1 (de) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
| US11078540B2 (en) | 2010-03-09 | 2021-08-03 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7572807B2 (en) | 2005-06-09 | 2009-08-11 | Bristol-Myers Squibb Company | Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
| US7579360B2 (en) | 2005-06-09 | 2009-08-25 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| PE20121506A1 (es) * | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| EP2086973B1 (de) * | 2006-10-11 | 2012-01-25 | Amgen Inc., | Imidazo- und triazolopyridinverbindungen und verfahren zu deren anwendung |
| EP2089359A2 (de) | 2006-10-31 | 2009-08-19 | Takeda Pharmaceutical Company Limited | Inhibitoren von mapk-erk-kinase |
| JO2985B1 (ar) | 2006-12-20 | 2016-09-05 | Takeda Pharmaceuticals Co | مثبطات كينازmapk/erk |
| KR20090111847A (ko) * | 2007-01-19 | 2009-10-27 | 아디아 바이오사이언스즈 인크. | Ｍｅｋ 억제제 |
| US8119658B2 (en) | 2007-10-01 | 2012-02-21 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| CA2705452C (en) | 2007-11-12 | 2016-05-31 | Takeda Pharmaceutical Company Limited | Mapk/erk kinase inhibitors |
| AU2008343065B2 (en) | 2007-12-19 | 2012-04-05 | Genentech, Inc. | 5-anilinoimidazopyridines and methods of use |
| NZ585306A (en) * | 2007-12-19 | 2012-05-25 | Genentech Inc | 8-Anilinoimidazopyridines and their use as anti-cancer and/or anti-inflammatory agents |
| US8557809B2 (en) | 2008-08-19 | 2013-10-15 | Array Biopharma Inc. | Triazolopyridine compounds as PIM kinase inhibitors |
| US8895550B2 (en) | 2008-08-19 | 2014-11-25 | Array Biopharma Inc. | Triazolopyridine compounds as PIM kinase inhibitors |
| US8987251B2 (en) | 2008-08-19 | 2015-03-24 | Array Biopharma Inc. | Triazolopyridine compounds as PIM kinase inhibitors |
| TWI496779B (zh) | 2008-08-19 | 2015-08-21 | Array Biopharma Inc | 作為ｐｉｍ激酶抑制劑之三唑吡啶化合物 |
| SG192944A1 (en) | 2011-02-25 | 2013-09-30 | Array Biopharma Inc | Triazolopyridine compounds as pim kinase inhibitors |
| WO2015081280A1 (en) * | 2013-11-26 | 2015-06-04 | Coferon, Inc. | Bromodomain ligands capable of dimerizing in an aqueous solution |
| US9670210B2 (en) | 2014-02-13 | 2017-06-06 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| TWI720451B (zh) | 2014-02-13 | 2021-03-01 | 美商英塞特控股公司 | 作為lsd1抑制劑之環丙胺 |
| WO2015123437A1 (en) | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
| EP3392244A1 (de) | 2014-02-13 | 2018-10-24 | Incyte Corporation | Cyclopropylamine als lsd1-inhibitoren |
| TWI687419B (zh) | 2014-07-10 | 2020-03-11 | 美商英塞特公司 | 作為ｌｓｄ１抑制劑之咪唑并吡啶及咪唑并吡嗪 |
| US9695167B2 (en) | 2014-07-10 | 2017-07-04 | Incyte Corporation | Substituted triazolo[1,5-a]pyridines and triazolo[1,5-a]pyrazines as LSD1 inhibitors |
| US9758523B2 (en) | 2014-07-10 | 2017-09-12 | Incyte Corporation | Triazolopyridines and triazolopyrazines as LSD1 inhibitors |
| WO2016007736A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Imidazopyrazines as lsd1 inhibitors |
| EA201792205A1 (ru) | 2015-04-03 | 2018-02-28 | Инсайт Корпорейшн | Гетероциклические соединения как ингибиторы lsd1 |
| AU2016306555B2 (en) | 2015-08-12 | 2021-01-28 | Incyte Holdings Corporation | Salts of an LSD1 inhibitor |
| US20190008859A1 (en) | 2015-08-21 | 2019-01-10 | Acerta Pharma B.V. | Therapeutic Combinations of a MEK Inhibitor and a BTK Inhibitor |
| US10166221B2 (en) | 2016-04-22 | 2019-01-01 | Incyte Corporation | Formulations of an LSD1 inhibitor |
| WO2020047198A1 (en) | 2018-08-31 | 2020-03-05 | Incyte Corporation | Salts of an lsd1 inhibitor and processes for preparing the same |
| EP3942045A1 (de) | 2019-03-21 | 2022-01-26 | Onxeo | Dbait-molekül in kombination mit einem kinaseinhibitor zur behandlung von krebs |
| EP4054579A1 (de) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Verfahren zur behandlung von krebsarten, die resistenz gegen kinase-inhibitoren erworben haben |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| US11492362B1 (en) | 2022-02-17 | 2022-11-08 | King Abdulaziz University | Pyridine derivatives for the treatment of hyperproliferative diseases |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007504241A (ja) * | 2003-09-03 | 2007-03-01 | アレイ バイオファーマ、インコーポレイテッド | 複素環式ｍｅｋ阻害剤、及びその使用方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE344791T1 (de) * | 1997-07-01 | 2006-11-15 | Warner Lambert Co | 2-(4-brom or 4-iod phenylamino)benzoesäurederivate und ihre anwendung als mek-inhibitoren |
| PL401637A1 (pl) * | 2002-03-13 | 2013-05-27 | Array Biopharma Inc. | N3 alkilowane pochodne benzimidazolu jako inhibitory MEK |
| PA8569201A1 (es) * | 2002-03-13 | 2004-05-21 | Array Biopharma Inc | "derivados de bencimidazol n3 alquilado como inhibidores de mek" "n3 alkylated benzimimidazole derivatives as mek inhibitors" |
| US20050049276A1 (en) * | 2003-07-23 | 2005-03-03 | Warner-Lambert Company, Llc | Imidazopyridines and triazolopyridines |
-
2005
- 2005-12-01 AU AU2005311451A patent/AU2005311451A1/en not_active Abandoned
- 2005-12-01 US US11/791,799 patent/US20070299103A1/en not_active Abandoned
- 2005-12-01 JP JP2007543779A patent/JP2008521858A/ja active Pending
- 2005-12-01 AT AT05826556T patent/ATE443063T1/de not_active IP Right Cessation
- 2005-12-01 CA CA002586796A patent/CA2586796A1/en not_active Abandoned
- 2005-12-01 WO PCT/EP2005/012855 patent/WO2006058752A1/en active Application Filing
- 2005-12-01 EP EP05826556A patent/EP1828184B1/de active Active
- 2005-12-01 DE DE602005016718T patent/DE602005016718D1/de active Active
- 2005-12-01 ES ES05826556T patent/ES2330872T3/es active Active
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2007
- 2007-05-21 IL IL183340A patent/IL183340A0/en unknown
- 2007-07-02 NO NO20073393A patent/NO20073393L/no not_active Application Discontinuation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007504241A (ja) * | 2003-09-03 | 2007-03-01 | アレイ バイオファーマ、インコーポレイテッド | 複素環式ｍｅｋ阻害剤、及びその使用方法 |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| US9084781B2 (en) | 2008-12-10 | 2015-07-21 | Novartis Ag | MEK mutations conferring resistance to MEK inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| US8637246B2 (en) | 2010-02-25 | 2014-01-28 | Dana-Farber Cancer Institute, Inc. | BRAF mutations conferring resistance to BRAF inhibitors |
| US9279144B2 (en) | 2010-02-25 | 2016-03-08 | Dana-Farber Cancer Institute, Inc. | Screening method for BRAF inhibitors |
| EP3028699A1 (de) | 2010-02-25 | 2016-06-08 | Dana-Farber Cancer Institute, Inc. | Braf-mutationen für resistenz gegen braf-inhibitoren |
| US11078540B2 (en) | 2010-03-09 | 2021-08-03 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1828184A1 (de) | 2007-09-05 |
| CA2586796A1 (en) | 2006-06-08 |
| US20070299103A1 (en) | 2007-12-27 |
| WO2006058752A1 (en) | 2006-06-08 |
| EP1828184B1 (de) | 2009-09-16 |
| NO20073393L (no) | 2007-09-03 |
| ES2330872T3 (es) | 2009-12-16 |
| ATE443063T1 (de) | 2009-10-15 |
| AU2005311451A1 (en) | 2006-06-08 |
| DE602005016718D1 (de) | 2009-10-29 |
| IL183340A0 (en) | 2007-09-20 |
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